Primary intracerebral hemorrhage: pathophysiology

We here review the pathophysiology of primary intracerebral hemorrhage to compare and contrast bleeds due to hypertension and congophilic angiopathy. Hypertension is characterized by early proliferation of arteriolar smooth muscle, followed later by apoptotic smooth muscle cell death and collagen deposition. Eventually excess or deficient collagen deposition can lead respectively to arteriolar occlusion, ectasia or both. Collagen has no contractile capability and is brittle, unable to withstand breakage due to pulse pressure. Arterioles physiologically bring down both blood pressure and pulse pressure, but excessive dilatation results in Charcôt-Bouchard aneurysms, which are fusiform, not saccular structures. The distribution of hypertensive hemorrhage reflects the high pulse pressure of arterioles immediately downstream from major end arteries with minimal intervening branching. Cerebrovascular amyloidosis is a stagnant beta-fibrillosis of arterioles, arising from failure of brain egress of beta-amyloid, after amyloid precursor protein cleavage within brain parenchyma. The lobar distribution of changes reflect an impairment of amyloid removal from brain interstitial fluid and Virchow-Robin spaces. Both diseases cause similar brittle arterioles with poor contractile capability, likely accounting for early growth of hematomas when they rupture. Fibrin globes form in concentric spheres and attempt to seal off the site of bleeding. The size of the final sphere of blood at cessation of bleeding determines the clinical spectrum, from asymptomatic to fatal. Since arteriolar bleeding is slower than arterial bleeding, several hours exist where intervention may be useful with recombinant factor VIIa or other therapies. We speculate on the importance of pulse pressure in the etiology of hemorrhage and resolve the debate over the existence of Charcot-Bouchard aneurysms. The high pulse pressure and brisk interstitial fluid pumping in Virchow-Robin spaces deep within the brain selectively protects against amyloidosis, while leaving these basal arterioles vulnerable to hypertensive damage. Hypertensive hemorrhages occur deep within the centrencephalon, while amyloid hemorrhages occur in a lobar distribution, where pulse pressure and bulk flow are less, away from the major feeding vessels of the brain. The brain distributions of hypertensive and of amyloid hemorrhages are thus different and complementary.